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Fycompa: novel anticonvulsant for partial-onset seizures

Fycompa (perampanel) is a new option for adjunctive therapy in partial-onset seizures with or without secondary generalisation.

Fycompa is available in six different strengths and is administered as a single daily dose at bedtime.

PHARMACOLOGY

Perampanel is the first in a new class of anticonvulsants, acting as a selective non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Activation of AMPA receptors by glutamate is thought to be responsible for most fast excitatory synaptic transmission in the brain, and plays a key part in the generation and spread of epileptic activity. However, the precise mechanism by which perampanel exerts its antiepileptic effects is not yet clear.1,2

CLINICAL STUDIES

The clinical efficacy and safety of perampanel as adjunctive therapy were assessed in three 19-week, double-blind studies in adults and adolescents (≥12 years) with partial-onset seizures with or without secondary generalisation, who were not adequately controlled with one to three anticonvulsants.2–4

Pre-treatment seizure frequency was assessed in all participants over a six-week baseline period, during which they were required to have more than five seizures and no seizure-free period exceeding 25 days. Patients in the first two studies were then randomised to receive once-daily perampanel 8mg or 12mg or placebo2,3 while those in the third study received once-daily perampanel 2mg, 4mg or 8mg or placebo.4 Treatment with up to three concomitant anticonvulsants was continued throughout.

The primary study endpoints were 50% responder rate (proportion of patients who had a ≥50% reduction in seizure frequency per 28 days relative to baseline) and per cent change in seizure frequency (per 28 days relative to baseline).2–4

In the first study (n=387), the median per cent change in seizure frequency was significantly greater in the perampanel 8mg and 12mg groups (-26.3% and -34.5%, respectively) than in the placebo group (-21.0%, p=0.0261 and p=0.0158, respectively). Fifty per cent responder rates were also greater with perampanel 8mg or 12mg (37.6% and 36.1%, respectively) than placebo (26.4%), although these differences were not significant (p=0.0760 and p=0.0914, respectively).2

Similar results were seen in the second study (n=321), although improvements in the 50% responder rate for the 8mg and 12mg doses over placebo were also significant (33.3% and 33.9% versus 14.7%, p=0.002 and p<0.001, respectively). The median per cent change in seizure frequency was -30.5% in the 8mg group and -17.6% in the 12mg group compared with -9.7% in the placebo group (p<0.001 and p=0.011, respectively).3

In the third study (n=623), significant improvements in the two primary endpoints over placebo were observed for the 4mg and 8mg doses of perampanel but not for the 2mg dose, indicating that the minimum effective dose is 4mg daily.4

Perampanel was generally well tolerated in all three studies, with dizziness and somnolence the most commonly observed adverse effects.2–4

The long-term safety and tolerability of perampanel were assessed in an open-label extension study involving patients who had completed one of the three initial double-blind studies. Most (91.4%) of the 1,186 patients were titrated to 10mg or 12mg daily, with a median duration of exposure of 51.4 weeks.5

Treatment-emergent adverse effects were observed in 87.4% of patients. As in the earlier studies, the most commonly observed adverse effects included dizziness, somnolence, headache and fatigue. Serious adverse effects were reported in 13.2% of patients and were primarily related to seizures.5

Results from this study also showed a consistent decline in seizure frequency over the first 26 weeks of treatment, which was maintained over at least one year of treatment.5

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